Analysis of the association between urinary glyphosate exposure and fatty liver index: a study for US adults.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a prevalent condition that often goes unrecognized in the population, and many risk factors for this disease are not well understood. Glyphosate (GLY) is one of the most commonly used herbicides worldwide, and exposure to this chemical in the environment is significant. However, studies exploring the association between GLY exposure and NAFLD remain limited. Therefore, the aim of this study was to assess the association between urinary glyphosate (uGLY) level and fatty liver index (FLI) using data from the National Health and Nutrition Examination Survey (NHANES), which includes uGLY measurements. METHODS: The log function of uGLY was converted and expressed as Loge(uGLY) with the constant "e" as the base and used for subsequent analysis. The association between Loge(uGLY) (the independent variable) level and FLI (the dependent variable) was assessed by multiple linear regression analysis. Smoothing curve fitting and a generalized additive model were used to assess if there was a nonlinear association between the independent and the dependent variables. A subgroup analysis was used to find susceptible individuals of the association between the independent variable and the dependent variable. RESULTS: A final total of 2238 participants were included in this study. Participants were categorized into two groups (< -1.011 and ≥ -1.011 ng/ml) based on the median value of Loge(uGLY). A total of 1125 participants had Loge(uGLY) levels ≥ -1.011 ng/ml and higher FLI. The result of multiple linear regression analysis showed a positive association between Loge(uGLY) and FLI (Beta coefficient = 2.16, 95% CI: 0.71, 3.61). Smoothing curve fitting and threshold effect analysis indicated a linear association between Loge(uGLY) and FLI [likelihood ratio(LLR) = 0.364]. Subgroup analyses showed that the positive association between Loge(uGLY) and FLI was more pronounced in participants who were female, aged between 40 and 60 years, had borderline diabetes history, and without hypertension history. In addition, participants of races/ethnicities other than (Mexican American, White and Black) were particularly sensitive to the positive association between Loge(uGLY) and FLI. CONCLUSIONS: A positive linear association was found between Loge(uGLY) level and FLI. Participants who were female, 40 to 60 years old, and of ethnic backgrounds other than Mexican American, White, and Black, deserve more attention.

FBXO11 amplifies type I interferon signaling to exert antiviral effects by facilitating the assemble of TRAF3-TBK1-IRF3 complex.

As the key component of host innate antiviral immunity, type I interferons (IFN-Is) exert multiple antiviral effects by inducing hundreds of IFN-stimulated genes. However, the precise mechanism involved in host sensing of IFN-I signaling priming is particularly complex and remains incompletely resolved. This research identified F-box protein 11 (FBXO11), a component of the E3-ubiquitin ligase SKP/Cullin/F-box complex, acted as an important regulator of IFN-I signaling priming and antiviral process against several RNA/DNA viruses. FBXO11 functioned as an essential enhancer of IFN-I signaling by promoting the phosphorylation of TBK1 and IRF3. Mechanistically, FBXO11 facilitated the assembly of TRAF3-TBK1-IRF3 complex by mediating the K63 ubiquitination of TRAF3 in a NEDD8-dependent manner to amplify the activation of IFN-I signaling. Consistently, the NEDD8-activating enzyme inhibitor MLN4921 could act as a blocker for FBXO11-TRAF3-IFN-I axis of signaling. More significantly, examination of clinical samples of chronic hepatitis B virus (HBV) infection and public transcriptome database of severe acute respiratory syndrome coronavirus-2-, HBV-, and hepatitis C virus-infected human samples revealed that FBXO11 expression was positively correlated with the stage of disease course. Taken together, these findings suggest that FBXO11 is an amplifier of antiviral immune responses and might serve as a potential therapeutic target for a number of different viral diseases.

Association of weight-adjusted-waist index with non-alcoholic fatty liver disease and liver fibrosis: a cross-sectional study based on NHANES.

AIM: The purpose of this study was to explore the association of weight-adjusted-waist index (WWI) with non-alcoholic fatty liver disease (NAFLD) and liver fibrosis. METHODS: A cross-sectional study including 6587 participants was conducted in the National Health and Nutrition Examination Survey (NHANES). Multiple linear regression was used to validate the association of WWI with NAFLD and liver fibrosis, and smoothed curve fitting and threshold effect models were used to validate non-linear relationships. Subgroup analyses were used to verify the stability of the relationship between the independent and dependent variables in different populations. RESULTS: There was a positive association of WWI with NAFLD and liver fibrosis. In the model adjusted for all covariates, the effect values of WWI with NAFLD and liver fibrosis were (OR = 3.44, 95% CI: 3.09-3.82) and (OR = 2.40, 95% CI: 2.05-2.79), respectively. This positive correlation became more significant as WWI increased when WWI was presented in quartiles (P for trend < 0.01). Smoothed curve fitting and threshold effects analysis suggested a non-linear correlation between WWI and NAFLD (LLR < 0.01), with the positive correlation between WWI and NAFLD becoming more significant when WWI was less than 11.44 [5.93 (95% CI: 5.04-6.98)]. However, there was a linear correlation between WWI and liver fibrosis (LLR = 0.291). When subgroup analyses were performed by indicators such as age, race and gender, we found that the positive association between WWI and the dependent variables (NAFLD and liver fibrosis) was more pronounced in white male participants aged < 40 years. CONCLUSIONS: Among adults in the United States, WWI was positively associated with the prevalence of NAFLD and liver fibrosis. Participants with a WWI less than 11.44 should be cautious about the possibility of an increased risk of NAFLD development due to a higher WWI. Meanwhile, white males younger than 40 years of age should be more cautious about the higher risk of NAFLD and liver fibrosis that might be associated with an increased WWI.

The association between blood manganese and liver stiffness in participants with chronic obstructive pulmonary disease: a cross-sectional study from NHANES 2017-2018.

BACKGROUND: To explore the relationship between blood manganese and liver stiffness in the United States among participants with chronic obstructive pulmonary disease (COPD). METHODS: All data were obtained from the 2017-2018 National Health and Nutrition Examination Survey database (NHANES). A total of 4690 participants were included in the study. All participants included complete information on COPD, liver stiffness, and blood manganese. Liver stiffness (kPa) was measured from "Examination Date" and blood manganese (ug/L) was obtained from "Laboratory Data". A multiple linear regression model was used to assess the correlation between blood manganese and liver stiffness. RESULTS: Among the 4690 participants, blood manganese was lower in the COPD group but liver stiffness was higher (p < 0.05). There was a positive correlation between blood manganese and liver stiffness (ß = 0.08, 95% CI 0.03, 0.12). This positive association was more pronounced in COPD participants (ß = 0.25, 95% CI 0.08, 0.42) and there was a non-linear relationship, which was more significant when blood manganese exceeded 14.43 ug/L (ß = 1.76, 95% CI 1.10, 2.41). CONCLUSIONS: The association between blood manganese and liver stiffness was positive, which was more apparent in COPD patients.

The association of asthma duration with body mass index and Weight-Adjusted-Waist index in a nationwide study of the U.S. adults.

BACKGROUNDS: The association between obesity and asthma has been of interest, but whether the duration of asthma has an effect on obesity is still limitedly studied. AIM: The purpose of this study was to investigate the association between asthma duration and obesity-related indexes, where obesity-related indexes include Body mass index (BMI) and Weight-adjusted-waist index (WWI). METHODS: Data from National Health and Nutrition Examination Survey (NHANES) 2009-2018 were obtained to conduct this cross-sectional study. Duration of asthma was used as the independent variable and obesity-related indexes as the response variables. Multiple linear regression was used to assess the association between the independent variable and the response variables, and subsequently smoothed curve fitting and threshold effect analysis were performed to clarify whether there was a nonlinear correlation between the independent variable and the response variables. Finally, subgroup analysis was conducted to find sensitive populations. RESULTS: A total of 9170 participants were included in the analysis. Asthma duration was statistically different between the two groups when all participants were grouped by median WWI (Q1 < 11.65, Q2 ≥ 11.65) (P < 0.001), but not by median BMI (Q1 < 31.8, Q2 ≥ 31.8) (P = 0.130). There was a positive association between asthma duration and WWI [ß = 0.016, 95% CI (0.016, 0.017)], but a negative one with BMI [ß = - 0.098, 95% CI (- 0.112, - 0.085)], and the correlations between the independent and response variables became more pronounced with increasing asthma duration (P for trend < 0.01). In addition, there were nonlinear relationships between asthma duration with BMI and WWI (log likelihood ratio < 0.001), with the best valid inflection points for asthma duration being 2 years (with WWI as the response variable) and 3 years (with BMI as the response variable), respectively. In the subgroup analysis, the positive association between asthma duration and WWI was more pronounced in the participants who were male, aged less than 40 years, and had asthma onset before 12 years of age. In contrast, when BMI was used as the response variable, the negative association between it and asthma duration was more pronounced among participants of female, aged 60 years or older, and with asthma onset less than 12 years of age. CONCLUSIONS: In US adults, asthma duration might cause changes in obesity-related indexes. Longer asthma duration might cause weight loss, but might increase the risk of abdominal obesity.

Blood Lead Exposure and Association With Hepatitis B Core Antibody in the United States: NHANES 2011-2018.

The objective of this project was to explore the distribution and related factors of blood lead and the association between blood lead and hepatitis B core antibody (HBcAb). All the data were from the U.S. National Health and Nutrition Examination Survey (NHANES). In total, 15,097 (aged 20-80 years) participants were included. Participants without a history of blood transfusion were more likely to be exposed to lower levels of blood lead [-2.30 (-3.13, -1.47) for HBcAb (-) and -2.23 (-4.54, 0.08) for HBcAb (+)]. The odds ratio (OR) of HBcAb (+) increased with blood lead and the result was 1.09 (1.06, 1.12). This study showed that older adults, men, people with a lower education level, a lower ratio of family income to poverty (PIR), a lower body mass index (BMI), or a history of blood transfusion, people who lived with a companion or with a total number of people in the family >3, people living in the United States for a longer time, U.S. citizens by birth or naturalization, and people not born in the United States were associated with higher blood lead exposure, and blood lead had a positive association with HBcAb (+).

The association between Herpes simplex virus type 2 and asthma: A cross-sectional study from National Health and Nutrition Examination Survey 1999-2016.

Background: The association between Herpes simplex virus type 2 (HSV-2) infection, a common infectious disease that increases the incidence of multisystem diseases, and asthma was less well studied. The aim of this study was to investigate the association between HSV-2 infection and the prevalence of asthma. Materials and methods: We used data from National Health and Nutrition Examination Survey (NHANES) 1999-2016 for analysis. The study population included was limited to those aged 20-45 years and contained complete information on HSV-2 infection and asthma. We calculated the prevalence of HSV-2, asthma, and HSV-2 combined with asthma separately. The association between HSV-2 infection and asthma was analyzed using multiple logistic regression. We also performed stratified analyses to reduce bias and to find sensitive cohorts. Results: The prevalence of HSV-2 infection was decreasing with change in time period (P for trend < 0.01), but the prevalence of asthma was increasing (P for trend < 0.01). The prevalence of HSV-2 infection was higher in those with asthma than in non-asthma participants. A positive association was found between HSV-2 infection and asthma [odds ratio (OR) = 1.15, 95% CI: 1.04-1.27]. Subgroup analysis showed that this positive association was more pronounced in participants who were male, White, 30 years ≤ age ≤ 40 years, body mass index (BMI) ≤ 28 kg/m2, 1.39 ≤ ratio of family income to poverty (PIR) < 3.49 and smokers. Conclusion: There was a positive association between HSV-2 infection and asthma, and participants who were male, White race, 30 years ≤ age < 40 years, BMI ≥ 28 kg/m2, 1.39 ≤ PIR < 3.49, and smokers should receive more attention.

Gene Signature and Prognostic Value of Ubiquitin-Specific Proteases Members in Hepatocellular Carcinoma and Explored the Immunological Role of USP36.

BACKGROUND: Ubiquitination is one of the most common post-translational modifications in cells and dysregulation is closely associated with the development of cancer. However, a comprehensive analysis of the role of ubiquitination in hepatocellular carcinoma (HCC) is still lacking. In this study we analyzed expression and prognostic value of Ubiquitin-Specific Proteases (USPs) in HCC, and the immunological role of USP36 in HCC. METHODS: Expression data, prognostic data, and DNA methylation data in cases of HCC were obtained from the cancer genome atlas (TCGA). Overexpression of USP36 in HCC was confirmed in the gene expression omnibus (GEO) database and verified by quantitative PCR in 10 pairs of HCC samples. ULCAN was used to analyze the correlation between USP36 and clinicopathological features. TIMER2.0 and DriverDBv3 were used to analyze the USP36 mutational profile. GSEA analysis explored the potential signaling pathways of USP36 affecting HCC. The immune and stromal scores of HCC samples were calculated using the ESTIMATE algorithm. TIMER1.0 was used to explore the correlation between USP36 and immune cell infiltration. Finally, we analyzed the correlation of USP36 expression with immune checkpoint molecules and determined the IC50 values of 6 chemotherapeutic drugs using the pRRophetic software package. RESULTS: Most USPs are abnormally expressed in HCC, among which USP36 and USP39 are most closely associated with HCC prognosis. We also found that USP36 is associated with TP53 mutational status. GSEA analysis indicated that USP36 may affect HCC progression through the dysregulation of various pathways such as ubiquitin-mediated proteolysis. USP36 expression positively correlated with both macrophage infiltration levels and multiple immune checkpoint molecules. Finally, chemosensitivity analysis indicated that chemosensitivity was lower in cells within the USP36 high expression group. CONCLUSIONS: Most USPs are abnormally expressed in HCC. Overexpression of USP36 in HCC is closely related to poor prognosis. In particular, the unique immunological role of USP36 may have potential clinical application value.

An Elevated METS-IR Index Is Associated With Higher Asthma Morbidity and Earlier Age of First Asthma in US Adults: Results Based on a Cross-Sectional Study.

Objective: The purpose of this study was to evaluate whether there is a correlation between the METS-IR index and asthma among Americans. Methods: In an attempt to establish the relationship between the METS-IR index and asthma prevalence and age at first onset of asthma, we conducted a logistic regression analysis, subgroup analysis, and dose-response curve analysis using the National Health and Nutrition Examination Survey (NHANES) database. Results: In model 3, each unit increase in METS-IR index led to 1.5% increase in asthma prevalence (OR= 1.015, 95% CI: 1.012, 1.018) and an earlier age of onset of asthma by 0.057years (ß= -0.057, 95% CI: -0.112, -0.002).Stratified analysis determined that an increase in METS-IR index was associated with asthma prevalence in almost all subgroups, except in the group where it was not known whether a blood relative had asthma, and a positive linear relationship was found between METS-IR index and asthma prevalence, as well as a linear negative relationship with age at asthma onset. Conclusion: Despite the fact that a direct causal relationship cannot be demonstrated, a higher METS-IR index is positively related to asthma prevalence and correspondingly may result in asthma onset at younger ages.

Relationship between hepatitis C and kidney stone in US females: Results from the National Health and Nutrition Examination Survey in 2007-2018.

Background: The main objective of this study is to explore the effects of hepatitis C (HCV) on the prevalence rate of kidney stones in US women. Method: Dates for HCV infection and kidney stones were collected from National Health and Nutrition Examination Survey (NHANES) database, a cross-sectional study. The analysis samples included adults aged ≥20 years and women from six consecutive cycles of the NHANES 2007-2018. The association between HCV infection and kidney stones was performed by using logistic regression models. Subgroup analyses were conducted to find sensitive crowds. Results: A total of 13,262 participants were enrolled, including 201 infected with HCV. After adjustment for potential confounders, we revealed a positive relationship between HCV and kidney stones (OR = 1.70, 95%CI:1.13-2.56). The crowds' statistically significant difference was characterized by other races (OR = 8.17, 95%CI:1.62-41.22) and BMI within 25-29.9 kg/m2 (OR = 2.45, 95%CI:1.24-4.83). Conclusions: HCV infection may affect the prevalence of urolithiasis in US women, even the causal relationship remains unclear, the relation deserves special attention. We considered such a study an ideal way to begin exploring the effects of HCV on kidney stones.

Machine learning models including insulin resistance indexes for predicting liver stiffness in United States population: Data from NHANES.

Background: Prevention and treatment of liver fibrosis at an early stage is of great prognostic importance, whereas changes in liver stiffness are often overlooked in patients before the onset of obvious clinical symptoms. Recognition of liver fibrosis at an early stage is therefore essential. Objective: An XGBoost machine learning model was constructed to predict participants' liver stiffness measures (LSM) from general characteristic information, blood test metrics and insulin resistance-related indexes, and to compare the fit efficacy of different datasets for LSM. Methods: All data were obtained from the National Health and Nutrition Examination Survey (NHANES) for the time interval January 2017 to March 2020. Participants' general characteristics, Liver Ultrasound Transient Elastography (LUTE) information, indicators of blood tests and insulin resistance-related indexes were collected, including homeostasis model assessment of insulin resistance (HOMA-IR) and metabolic score for insulin resistance (METS-IR). Three datasets were generated based on the above information, respectively named dataset A (without the insulin resistance-related indexes as predictor variables), dataset B (with METS-IR as a predictor variable) and dataset C (with HOMA-IR as a predictor variable). XGBoost regression was used in the three datasets to construct machine learning models to predict LSM in participants. A random split was used to divide all participants included in the study into training and validation cohorts in a 3:1 ratio, and models were developed in the training cohort and validated with the validation cohort. Results: A total of 3,564 participants were included in this study, 2,376 in the training cohort and 1,188 in the validation cohort, and all information was not statistically significantly different between the two cohorts (p > 0.05). In the training cohort, datasets A and B both had better predictive efficacy than dataset C for participants' LSM, with dataset B having the best fitting efficacy [±1.96 standard error (SD), (-1.49,1.48) kPa], which was similarly validated in the validation cohort [±1.96 SD, (-1.56,1.56) kPa]. Conclusions: XGBoost machine learning models built from general characteristic information and clinically accessible blood test indicators are practicable for predicting LSM in participants, and a dataset that included METS-IR as a predictor variable would improve the accuracy and stability of the models.